I have been treating patients with type 2 diabetes and hypogonadism for nearly 15 or more years. This is a population in which there is a high prevalence of hypogonadism, functional hypogonadism due to insulin resistance, obesity and so on, and they really have sexual symptoms and problems, and when we can prove that they are really hypogonadal like with low free testosterone, because they might have low total testosterone but not low free testosterone, and if they have sexual problems, then we start treating them.
We have done quite a few studies but the last one was really a placebo-controlled, lasted two years, and was done on type 2 diabetic patients with obesity and proven hypogonadism. And it was interesting to see that glycemic control improved, glycated hemoglobin went down significantly during the first year of treatment when only testosterone group was on testosterone, but then the second year in the placebo group, glycated hemoglobin went down as well, and in the second year of testosterone treatment, glycated hemoglobin even further decreased which means that with longer treatment with testosterone, metabolic effects were more and more pronounced. The same dynamics have been seen in insulin sensitivity, we measured HOMA insulin resistance index, and also observed a significant drop in HOMA IR during the first year and additional drop during the second year in the testosterone group, and of course in the placebo group when they were switched to testosterone also a significant reduction of insulin resistance and amelioration of insulin sensitivity.
As type 2 diabetic patients have an increased risk of cardiovascular disease and cardiovascular mortality, we decided to also look to the early atherosclerotic changes on arteries. We measured flow-mediated dilation of the brachial artery, so we looked for the functional changes. We saw impaired flow-mediated dilation of the brachial artery at the beginning, and after one year of testosterone replacement therapy, this ameliorated significantly so dilation of the brachial artery was better after one year, and the same happened in the placebo group. But here during the second year of the testosterone treatment, there was no additional amelioration, so changes in functional matters happen early and they are sustained then. And then we also measured the early morphological changes of atherosclerosis, so the intermediate sickness of the carotid arteries, and we have seen a decrease of intermediate sickness, a significant decrease after the first year, and additional decrease after the second year of testosterone replacement therapy in type diabetic men who were obese.
I am a great believer in lifestyle changes or in healthy lifestyle, so physical activity, healthy diet, but a group from our hospital recently, I think a few weeks ago, published a study where they looked into obese diabetic men who were treated with GLP-1 agonists at the dosage to treat obesity, and they compared this group with a group that was treated with testosterone. Of course, they found a good effect on body weight with GLP-1 agonist, which is obvious, but other effects, in spite of huge drop in body weight, were not so pronounced as in the group that was on testosterone. So metabolic effects okay, but other important effects of testosterone were not shown only with weight reduction and GLP-1 reduction. So I think that you can achieve a lot, you can achieve improvement in testosterone levels, it has been shown, within free testosterone levels, but probably adding testosterone in those patients who have sexual symptoms, which are really needed to make a diagnosis of hypogonadism, could add on a beneficial effect.
The question is arising, due to the high prevalence of hypogonadism in the population of type 2 diabetic men with obesity or with overweight, whether to introduce a regular measurement of testosterone levels in these patients. I think this would be exaggeration because we have 0.4 billion people who have type 2 diabetes globally, and half of them are probably men, so I would suggest that we should measure testosterone in patients who have sexual symptoms, because having sexual symptoms like low libido, poor morning erections, or erectile dysfunction is prerequisite to make a diagnosis of hypogonadism. Without these symptoms, we can’t speak about hypogonadism, and we are not allowed to treat patients with testosterone. So physicians, healthcare professionals, should focus on asking these questions, and in those patients who have these problems, it is correct and the testosterone levels should be measured. Very importantly in obese type 2 diabetic patients, we should calculate free testosterone because nearly half of patients with type 2 diabetes who are obese have low total testosterone levels, but to really prove hypogonadism in them, we have to calculate free testosterone, which is not low in more than one-third of patients or maybe even less in some cohorts.
The diabetes guidelines, due to this high prevalence of hypogonadism in obese type 2 diabetic men, might include or some of them have already included the measurement of testosterone. As I said, it might be exaggeration, but there is more personal approach needed especially asking about sexual problems of patients, and then yes, and this should be figured how to put it into the guidelines, but I think it should be in the guidelines. It could help patients.
Prof. Dr. med. Marija Pfeifer Medical Faculty University of Ljubljana, Slovenia